Project Summary We have found that ?-catenin protein is highly up-regulated in disc tissues derived from patients with disc degeneration and have created a ?-catenin conditional activation mouse model which displays severe defects in disc tissue morphology and pain. ?-catenin plays a key role in the development of disc degeneration and one of the key signaling mechanisms is to activate Runx2 expression which subsequently regulates Mmp13 expression in Col2-expressing cells in disc tissue. In this study, we will determine the role of Runx2 and CCL2 in ?-catenin-induced disc degeneration